Liquid chromatograph mass spectrometer

ABSTRACT

A liquid chromatograph mass spectrometer is provided with an interface portion between a liquid chromatograph portion and a mass spectrometry portion. In the interface portion, an ionizing device is provided to ionize a liquid sample sent from the liquid chromatograph portion. Also, a desolvating device is provided to remove a solvent from the produced ions or charged droplets by the ionizing device. Then, the sample is introduced into the mass spectrometry portion. The interface portion has a plurality of ionizing devices for ionizing the liquid sample by different methods.

BACKGROUND OF THE INVENTION AND RELATED ART STATEMENT

[0001] The invention relates to a liquid chromatograph mass spectrometer(hereinafter referred to as “LC/MS”), and more particularly, to aninterface disposed between a liquid chromatograph portion and a massspectrometry portion of the LC/MS.

[0002] In an analytical method of the LC/MS, a component separated atthe liquid chromatograph portion is ionized under the atmosphericpressure, and introduced into the mass spectrometry portion. In thiscase, it is necessary to provide an interface for ionizing the componentseparated through a column in the liquid chromatograph portion. Theinterface generally used in the LC/MS includes an electrosprayionization method (hereinafter referred to as “ESI method”) and anatmospheric pressure chemical ionizing method (hereinafter referred toas “APCI method”).

[0003] In the ESI method, a liquid sample is introduced to a tip of athin nozzle, and a high voltage is applied to the tip of the nozzle. Asa result, a strong unequal electric field is formed at the tip of thenozzle, and the liquid sample is nebulized as charged droplets by thestrong electric field. Further, the droplets are divided by Coulombforce of ions in the droplets, thereby being ionized. On the other hand,in the APCI method, a gas flow in a nebulizer forces the liquid sampleto be nebulized. Then, the nebulized liquid sample is heated toevaporate solvent in the droplets. Thereafter, buffer ions are producedby the corona discharge to ionize the sample (chemical ionization).

[0004]FIG. 5 is a schematic view showing a general structure of aconventional LC/MS. A reference numeral 31 represents a liquidchromatograph portion, and a reference numeral 40 represents a massspectrometry portion. A reference numeral 50 represents an interfaceportion, which includes an electrospray ionizing portion 52 using theESI method. Also, a heating mechanism (not shown) is provided in thinpipes 54 disposed next to the electrospray ionizing portion 52 forfunctioning as a desolvation device to accelerate desolvation of thecharged droplets produced at the electrospray ionizing portion 52.

[0005] In the liquid chromatograph portion 31, the sample is injectedthrough a sample introduction portion 35. Then, a liquid supply pump 34supplies a mobile phase 33 to carry the sample to a column 36, and thesample is separated there. An electrospray probe 53 includes a pipethrough which the liquid sample is supplied from the liquidchromatograph portion 31. A front end of the pipe opposite to the thinpipes 54 is formed in a needle shape, so that the liquid passing throughthe pipe is sprayed through a nozzle portion of the needle shape frontend. Then, a high voltage generating circuit (not shown) applies a highvoltage in the order of several KV to the electrospray probe 53. Withthis structure, the liquid sample sent from the liquid chromatographportion 31 is drawn in a spray shape by a strong electric field formednear the nozzle of the front end of the needle. At this time, a part ofthe liquid sample becomes an ion and a charged droplet, and enters intothe thin pipes 54.

[0006] A heater in the thin pipes 54 heats the charged droplets toevaporate a solvent. The droplets are micronized further throughcollisions with other particles, thereby accelerating ionizationthereof. The ions thus produced are drawn out from the thin pipes 54 andsent to the mass spectrometry portion 40.

[0007] While passing through the thin pipes 54 as described above, thedesolvation and ionization of the liquid sample are accelerated, and theions thereof are introduced into the mass spectrometry portion 40. Themass spectrometry portion 40 is held in a reduced pressure state by arotary pump 44, and is held in a further reduced pressure state by turbomolecular pumps 45, 46. The ionized sample introduced into the reducedpressure state of the mass spectrometry portion 40 as described above isconverged by a lens effect of a convergent lens 42 and a quadruple polerod 43, and then the sample is analyzed.

[0008] On the other hand, when the APCI method is used for theionization, an atmospheric pressure chemical ionizing portion 60 shownin FIG. 6 is attached instead of the electrospray ionizing portion 52shown in FIG. 5. More specifically, the atmospheric pressure chemicalionizing portion 60 includes a pipe through which the liquid samplepasses; a probe 62 with a front end formed in a needle shape; anatomizing chamber 61 disposed to surround the needle portion of theprobe 62; and a discharge electrode 63 disposed in front of an openingof the atomizing chamber 61. A heater (not shown) heats the atomizingchamber 61, and also, a voltage in several KV is applied to thedischarge electrode 63. Thus, the liquid sample sent from the liquidchromatograph portion 31 is sprayed into the atomizing chamber 61through a nozzle at the front end of the needle of the probe 62 by anatomizing gas from a gas line connected separately to the probe, and thesolvent is heated and removed by the heater. Then, the liquid sample isionized through contact with the buffer ions produced at the dischargeelectrode. While the desolvation and the ionization of the ions andcharged droplets thus produced are accelerated in the same manner as inthe above-described ESI method, through the heated thin pipes 54, thesample is sent to the mass spectrometry portion 40.

[0009] As described above, in both ESI method and the APCI method,different ionizing portions are used. Thus, when the analysis is carriedout, the ionizing portion needs to be changed according to the method tobe used. Depending on a type of sample, either of the ESI method and theAPCI method is suitable for analyzing the sample. Therefore, it isnecessary to carry out the analysis using the ESI method or the APCImethod separately. For example, the APCI method is suitable foranalyzing a sample with a low polarity, and the ESI method is suitablefor a sample with a high polarity. Therefore, when a sample includes acomponent suitable for the ESI method and another component suitable forthe APCI method, the analysis needs to be carried out twice using theionizing portion for the ESI method and the ionizing portion for theAPCI method. Thus, it takes long time and high cost for the analysis.Also, when an unknown sample is analyzed, since it is not known whichionizing method should be used, both the ESI and APCI methods have to becarried out. Further, switching of the ionizing portions also takes timeand cost.

[0010] In view of the above problems, the present invention has beenmade and an object of the invention is to provide a liquid chromatographmass spectrometer (LC/MS), wherein an analysis can be carried out easilyin a short time without reviewing an ionizing method with respect to anunknown sample and without knowing characteristics of a sample to beanalyzed. In the invention, one analysis is sufficient even for a sampleincluding mixed components suitable for different ionizing methods,resulting in a shorter time at a lower cost.

[0011] Further objects and advantages of the invention will be apparentfrom the following description of the invention.

SUMMARY OF THE INVENTION

[0012] In order to solve the above problems, a liquid chromatograph massspectrometer (LC/MS) of the present invention is provided with aninterface portion between a liquid chromatograph portion and a massspectrometry portion. In the interface portion, an ionizing device isprovided for ionizing a liquid sample sent from the liquid chromatographportion. Also, a desolvating device is provided for removing a solventfrom the produced ions or charged droplets by the ionizing device. Then,the sample is introduced into the mass spectrometry portion. Accordingto the present invention, the interface portion has a plurality ofionizing devices for ionizing the liquid sample.

[0013] The interface portion has the plurality of the ionizing devicesso that both an electrospray ionization method (hereinafter referred toas “ESI method”) and an atmospheric pressure chemical ionizing method(hereinafter referred to as “APCI method”) can be applied. Thus, thesample can be ionized in one analysis while switching between the ESImethod and the APCI method. Also, in a case the switching is notnecessary, it is possible to obtain ions produced by both the ESI methodand the APCI method at the same time. Thus, without reviewing an optimumionizing method for the sample or without knowing characteristics of thesample to be analyzed, the analysis can be easily carried out in a shorttime.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014]FIG. 1 is a schematic view showing an embodiment of a liquidchromatograph mass spectrometer (LC/MS) according to the presentinvention;

[0015]FIG. 2 is a graph showing a result obtained by the LC/MS accordingto the invention;

[0016]FIG. 3(A) is a graph showing a result obtained by a conventionalLC/MS using an electrospray ionization (ESI) method;

[0017]FIG. 3(B) is a graph showing a result obtained by a conventionalLC/MS using an atmospheric pressure chemical ionizing (APCI) method;

[0018]FIG. 4 is a graph showing a result obtained by the LC/MS of theinvention;

[0019]FIG. 5 is a schematic view showing an interface portion of aconventional LC/MS using the ESI method; and

[0020]FIG. 6 is a schematic view showing an interface portion of aconventional LC/MS using the APCI method.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0021] Hereunder, an embodiment according to the present invention willbe explained with reference to the accompanying drawings. FIG. 1 is aschematic view for showing a liquid chromatograph mass spectrometer(LC/MS) of an embodiment according to the invention. The LC/MS includesa liquid chromatograph portion 1, an interface portion 3, a massspectrometry portion 7, pipings 9, 10, 11, and a splitter 13. Theinterface portion 3 is formed of an electrospray ionizing portion 4 andan atmospheric pressure chemical ionizing portion 5 in which a dischargeelectrode 6 is disposed.

[0022] A sample eluted from the liquid chromatograph portion 1 isdivided at the splitter 13 after passing through the piping 9, andintroduced to the electrospray ionizing portion 4 and the atmosphericpressure chemical ionizing portion 5 through the pipings 10, 11. At thistime, the splitter 13 adjusts a quantity of the liquid introduced intothe electrospray ionizing portion 4 and the atmospheric pressurechemical ionizing portion 5. The liquid sample introduced into theelectrospray ionizing portion 4 and the atmospheric pressure chemicalionizing portion 5 is ionized when a high voltage is applied to theatmospheric pressure chemical ionizing portion 5 and the dischargeelectrode 6 disposed at the electrospray ionizing portion 4, and thenled to the mass spectrometry portion 7.

[0023] When an analysis is carried out under a state where the highvoltage is applied simultaneously to the discharge electrodes 6 of theelectrospray ionizing portion 4 and the atmospheric pressure chemicalionizing portion 5, it is possible to obtain a result combined by theESI method and APCI method. The result thus measured is shown in FIG. 2.Also, the results obtained separately by the ESI and APCI methods areshown in FIGS. 3(A) and 3(B), respectively. In the conventional methodas shown in FIG. 3(A), the sample suitable for the ESI method can bedetected. However, the sample suitable for the APCI method can not bedetected. In the same manner, as shown in FIG. 3(B), while the samplesuitable for the APCI method can be detected, the sample suitable forthe ESI method can not be detected. Therefore, according to theconventional method, the measurement needs to be done twice. Accordingto the present invention, both samples suitable for the ESI method andthe APCI method can be detected, so that the analysis of the sample canbe carried just once.

[0024] By switching the high voltage applied between the electro sprayionizing portion 4 and the atmospheric pressure chemical ionizingportion 5, it is possible to obtain a result by the ESI method alone, aresult by the APCI method alone, or a result by both the ESI method andthe APCI method in one measurement. These results may be processed insynchronism with the switching of the high voltages. In other words, theions obtained during a time when the high voltage is applied to aspecific ionizing method can be processed as a result obtained by thespecific ionizing method. Therefore, it is possible to extract the ionscorresponding only to the specific ionizing method. For example, theanalysis may be carried out while switching between the ESI method, theAPCI method and both of the ESI and APCI methods every second.Accordingly, a result can be continuously obtained by the respectiveionizing methods, as shown in FIG. 4.

[0025] Hereinabove, the embodiment according to the present inventionhas been explained. However, the present invention is not limited to theabove embodiment and various changes can be made as long as they arewithin a scope of claims. For example, as the ionizing method, while theESI method and the APCI method are used, the ionizing method is notlimited thereto. Various ionizing methods, such as a fast atombombardment method (FAB method), can also be employed. Also, when theliquid sample is introduced to the electrospray ionizing portion 4 andthe atmospheric pressure chemical ionizing portion 5, a quantity of theliquid sample may be adjusted by disposing a resisting pipe to thepipings 10, 11, instead of the splitter 13 in the present embodiment.

[0026] According to the present invention, since the plurality of theionizing devices is provided in the interface portion, the analysis canbe carried out in a short time without optimizing the ionizing methodwith respect to a sample.

[0027] While the invention has been explained with reference to thespecific embodiments of the invention, the explanation is illustrativeand the invention is limited only by the appended claims.

What is claimed is:
 1. A liquid chromatograph mass spectrometer having aliquid chromatograph portion and a mass spectrometry portion,comprising: an interface portion provided between the liquidchromatograph portion and the mass spectrometry portion, said interfaceportion having a plurality of ionizing devices different from each otherfor ionizing a sample sent from the liquid chromatograph portion uponapplication of a voltage, and a desolvating device for desolvating thesample before introducing the sample to the mass spectrometry portion.2. A liquid chromatograph mass spectrometer according to claim 1,further comprising selecting means electrically connected to theionizing devices for selectively applying the voltage to at least one ofthe ionizing devices for actuating the same for measurement.
 3. A liquidchromatograph mass spectrometer according to claim 1, further comprisinga splitter disposed between the liquid chromatograph portion and theionizing devices for dividing the sample supplied from the liquidchromatograph portion, and for introducing the sample to each of theionizing devices.
 4. A liquid chromatograph mass spectrometer accordingto claim 3, wherein said plurality of ionizing devices includes electrospray ionizing portion and atmospheric pressure chemical ionizingportion.